Intro: psychopharmacology: study of effects of drugs on NS, behavior. Drug: exogenous chem not necessary
for normal cell function, alters functions of cells in low dose. Chem messengers produced by body are not
drugs, but synthetic chem that mimic affects are called drugs. Sites of action: points at which drug molecules
interact w/ molecules on/in cells of body, affecting some biochem processes of cells.
Principles of psychopharmacology: routes of administration of drugs and fate in body
Pharmacokinetics: drugs absorbed, distributed in body, metabolized (enzyme breakdown), excreted. To be
effective, drug must reach sites of action by entering CNS
o intravenous immediately enters blood, entire dose reaches brain in seconds, more skill
o intraperitoneal almost as quick, peritoneal cavity (around abdominal organs), common for lab
o intramuscular absorbed into blood via capillaries, can be mixed to constrict vessels, slow flow
o subcutaneous beneath skin, small amount, fat-soluble for slow absorption
o oral most common, not good for all chemicals since acid/enzymes might destroy, e.g. insulin
o sublingual under tongue, absorbed by capillaries to mucous membrane, e.g. nitroglycerine
o intrarectal suppository (opposite end of digestive tract, drugs that would upset stomach
o inhalation treating lung disorders, quick effects because of short route from lungs to brain
o topical steroid hormones, nicotine, mucous membrane of nasal passages, delivered to brain rapidly
o intracerebral: directly into brain to study effects in specific region of brain
o ICV: widespread dist., pass barrier by injecting into cerebral ventricle, absorb into brain tissue, antibiotics
o Dist. in body: rate to reach site of action affected by lipid solubility (barrier prevents water-soluble. Heroin
more lipid-soluble v. morphinefaster effects) depot binding: drug binds w/ tissues of body / proteins in
blood, can’t reach site / affect while bound. Albumin: protein in blood, transport free fatty acids, binds w/
lipid-soluble drugs. Binding delays effect, reaches brain when albumin full. Other binders - fat tissue, liver,
bones, muscle, slower since outside blood vessels, less likely to interfere w/ initial effects (e.g. thiopental)
o Deactivated by enzymes in liver/blood/brain, kidneys excrete. Can transform drug moleculesmore active
effectiveness: dose-response curve: magnitude of effect of drug as f(amount). Yes point of max effect.
Margin of safety: difference btwn curves for dif. effects of same drug (opiatesanalgesia, also depress
neuron activity in medulla that control heart rate/respiration). Therapeutic index: ratio btwn dose that
makes desired effect in 50% / toxic effect in 50% (e.g., if toxic dose 5x higher than effective doseindex =
5. Barbiturates = 2, tranquilizers = 100). Variation in effectiveness (1) dif. sites of action: morphine/aspirin
both analgesic, morphine affects spinal cord/brain; aspirin reduces amount of chem that transmits info from
damaged tissue to neurons) (2) affinity: readiness that 2 molecules join / for site of action. Higher affinity =
lower dose, same effect. Drug can have high affinities for some sites of action, low affinities for others, best
drug has high affinity for sites w/ therapeutic effects, low affinity for toxic sites
repeated admin: effects not constant, usually diminish: tolerance: withdrawal, opposite to drug (e.g.,
heroin euphoria vs. dysphoria, relax vs. agitate). When drug affects body systems, mechanisms produce opp.
reaction to compensate for disturbance, felt more when unopposed by drug. Mechanisms inc. dec. in binding
effectiveness (less affinity / fewer receptors), coupling of receptors to ion channels / 2 messenger less
effective. Some effects of drug may show tolerance while others don’t due to different sites of action. If
more effective, sensitization: repeated dose of druglarger effects, less common
placebo: innocuous substance w/o specific physiological effect, still has effect; used as control
Sites of Drug Action: most drugs affect behavior via synaptic transmission; antagonists block/inhibit
postsynaptic effects; agonists facilitate effect of neurotransmitter on postsynaptic cell.
Effects on NT production: 1 step is synthesis of NT from precursor; if rate of synthesis/NT release is inc.
when precursor admin’edagonist. Enzymes control synthesis steps, if drug inactivatesantagonist.
effects on NT storage/release: transporter molecules that fill vesicles can be blocked (bind+inactivate), no
NTantagonist, can prevent NT release by deactivating proteins that cause docked synaptic vesicles to
fuse w/ presynaptic membrane and expel contents, OR agonists bind w/ proteins, trigger NT release effects on receptors: most important site of action; drugs can bind here like NT, can be direct agonist:
mimics NT effects, binding causes ion channels to open, produce postsynaptic potentials, or receptor
blocker/direct antagonist: molecules bind to receptors, prevent NT from binding. Noncompetitive
binding: drug doesn’t interfere w/ binding site for principal ligand (NT). Indirect antagonist prevents ion
channel from opening (effect similar to direct; site of action different). Indirect agonist attaches to alt. site,
lets ion channel open. Antagonists activate presynaptic receptors (causes less NT release); agonists block
presynaptic autoreceptors (more NT release). Presynaptic heteroreceptors: in button, receives input from
another button via axoaxonic synapse, binds w/ NT released by presynaptic button, can block/facilitate
presynaptic inbhition/facilitation. When neurons w/ autoreceptors active, they release NT, which stimulates
autoreceptors on same dendrites, dec. neural firing via hyperpolarization (regulatory effect to prevent
overactivity). Drugs that activate dendritic autoreceptorsantagonists, those that blockagonists. Effects
depend on where receptor located, what normal effects are, whether drug activates receptors/blocks actions.
Effects on NT reuptake/destruction: termination of postsynaptic potential: drugs interfere w/ reuptake if
they inactivate transporter molecules, or interfere w/ destruction by binding w/ enzyme (agonists / AChE)
NTs and neuromodulators: many NT types, most glutamate (excitatory), GABA (inhibition), glycine (inhibition
in spinal cord/lower stem). All sense organs send info to brain via axons that release glutamate (except peptide).
Other NTs are modulating, activate/inhibit entire circuits of neurons involved in particular brain functions.
Acetylcholine: DON’T NEED TO KNOW HOW ITS MADE, OR CATCHELOMINES secreted by
efferent axons of CNS for muscular movement. Also in ganglia, organs of parasympathetic, in ANS. First
discovered since outside CNS. Synapses are acetylcholinergic b/c they release Ach. Effects in brain usually
facilitatory. In dorsolateral pons, responsible for REM. In basal forebrain, activate cerebral cortex, facilitate
(perceptual) learning. In medial septum, control electricity of hippocampus, modulate its functions
(memories). Ach made of choline (lipid breakdown), acetate (anion in vinegar). Actetate transferred from
acetyl-CoA enzyme (cofactor). With choline acetyltransferase, acetate transferred from acetyl-CoA to
cholineAch, CoA. Botulinum toxin: produced by clistridium botulinum, prevents release of Ach. Black
widow spider venom stimulates Ach release. Ach deactivated by ACHE in postsynaptic membrane, mak